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ERK activation, gene dysregulations and cell transformation at submicromolar doses of Cr6+ in C3H10T1/2 and BALB/c 3T3 cells: interaction with Lipoic acid

ABSTRACT: The molecular mechanism of Cr6+ carcinogenicity is not well understood. Studies advocate a key involvement of the altered cytogenomics and dysregulated pathways in Cr6+ toxicity. However, the dissimilarity in expression of genes and pathways in cells transformed by Cr6+ has led us to supplement more data on the subject. We report here genomics of cells transformed after acute exposure to submicromolar (0.01or1µM) test doses of Cr6+; the non-cytotoxic submicromolar test concentrations transformed the mammalian cells; the characteristic gain of anchorage independent growth potential was demonstrable in soft agar assay. C3H10T1/2 and BALB/c 3T3 cell transformation assay has been used which is established in literature as the in vitro carcinogenesis test system. Gene expression profile of the transformed cells was found to be dysregulated at both the toxicant doses. PARP1 gene was significantly up regulated and SFN, MTIF2, IRGQ, RAVER2, SLC2A6, MLLT3, EPB4.1L3, JAK1, RALGPS1, EXTL3, PRMT6, PREB, SERPINE1, MORC4 genes were significantly down regulated commonly at two test concentrations. These genes were found to be involved in tumour suppression, DNA repair, cell cycle control, energy metabolism and biosynthesis.Cr6+ also induced MAPK signalling via ERK phosphorylation. Activation of ERK signalling, dysregulation of gene expressions, and cell transformation was prevented by alpha lipoic acid (LA) in equimolar concentrations. The acute exposure to submicromolar concentrations of Cr6+ can induce cell transformation and gene dysregulations in mammalian cell. The influenced genes are crucial for progression of Cr6+ toxicity and their mitigation by LA shows critical role of redox reactions in Cr6+ toxicity.

ORGANISM(S): Mus musculus

PROVIDER: GSE43156 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA184732

REPOSITORIES: GEO

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ERK activation, gene dysregulations and cell transformation at submicromolar doses of Cr6+ in C3H10T1/2 and BALB/c 3T3 cells: interaction with Lipoic acid

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